Myeloid derived suppressor cells (MDSCs) are comprised of a mixture of immature myeloid cells such as granulocytes and monocyte-macrophages as well as myeloid cell precursors at various stages of differentiation. MDSCs are also known as immature myeloid cells, or IMCs. MDSCs were originally categorized as suppressor cells due to their ability to suppress the activation of T cells. It is believed that MDSCs function in part to protect the host from the harmful effects of excessive immune stimulation during acute and chronic infections, and to the limit the generation of autoimmune responses towards tissue antigens released by trauma.
MDSCs in mice are characterized as CD11b+Gr-1+ (Nagaraj, S., et al. Nat Med 13, 828-835 (2007); Nagaraj, S., Schrum, A. G., Cho, H. I., Celis, E. & Gabrilovich, D. I. J Immunol 184, 3106-3116 (2010); Nagaraj, S. & Gabrilovich, D. I. Cancer J 16, 348-353 (2010); Herber, D. L., et al. Nat Med 16, 880-886 (2010); Ramakrishnan, R., et al. J Clin Invest 120, 1111-1124 (2010)). The myeloid lineage differentiation antigen Gr-1 (Ly6G and Ly6C) is expressed on myeloid precursor cells, granulocytes, and transiently on monocytes (Youn, J. I., Nagaraj, S., Collazo, M. & Gabrilovich, D. I. J Immunol 181, 5791-5802 (2008)). The CD11b receptor (Mac-1) is an integrin that is expressed on the surface of monocytes/macrophages, dendritic cells (DC), granulocytes, and activated B- and T-lymphocytes. Gr-1++CD11b+ cells represent 30-40% of normal bone marrow cells and 2-4% of all nucleated normal splenocytes. In humans, MDSCs are characterized in humans as Lin−HLADR−CD33+′. CD33 is also referred to as siglec-3. There may be different subsets of MDSCs as evidenced by heterogeneous expression of CD14 and CD15 in MDSC populations.
Although the action MDSCs may be beneficial in dampening certain autoimmune responses, the proliferation of MDSCs is associated with activation of these cells in a pathological context. Activation is mediated through several transcription factors and results in the up regulation and expression of immunosuppressive factors such as ARG1 and NOS2, up regulation of activity of the NADPH oxidase complex, and an increase in the production of NO, ROS, RNS, and cytokines. During chronic inflammation in particular, the accumulation of MDSC leads to a sustained immunosuppressive environment that inhibits the process of differentiation/maturation (Nagaraj, S., et al. Nat Med 13, 828-835 (2007); Movahedi, K., et al. Blood 111, 4233-4244 (2008); Nagaraj, S., et al. Nat Med 13, 828-835 (2007); Kusmartsev, S., Nefedova, Y., Yoder, D. & Gabrilovich, D. I. J Immunol 172, 989-999 (2004)). The inability of the host system to mount an effective immune response is one of the major factors responsible for tissue injury in chronic inflammation. MDSCs also play one of the major roles in tumor associated immune abnormalities and other infections.